Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy.

Activities of the gamma-aminobutyric acid (GABA) and cholinergic nerve-terminal marker enzymes glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) as well as the astrocytic enzyme glutamine synthetase (GS) were measured in homogenates of dissected brain tissue obtained at autopsy from nine cirrhotic patients dying in hepatic encephalopathy and an equal number of control subjects matched for age, agonal status, and time interval from death to freezing of autopsied material. GAD activities varied as a function of agonal status in control samples, confirming a previous report, but were unchanged in brain tissue from cirrhotic patients, suggesting no loss of integrity of presynaptic GABA nerve terminals in this disease. On the other hand, GS activities were selectively decreased by 25% (P less than 0.01) in caudate nuclei of cirrhotic patients, reflecting, no doubt, the severe astrocytosis consistently observed in this brain structure. CAT activities, expressed per milligram of protein, were found to be increased by 30% (P less than 0.01) in the prefrontal cortex of cirrhotic patients. Whether such changes result from a relative increase in CAT as a consequence of losses of astrocytic protein or reflect altered cholinergic function in hepatic encephalopathy associated with chronic liver disease awaits further study.